一氧化氮诱导海马神经元凋亡信号通路的研究  

Nitric oxide mediating kinase signal pathway involves in hippocampus neuron ischemia-reperfusion injury

作　　者：李薇[1] 赵光瑜[2] 邵建林[3] 

机构地区：[1]昆明医学院第一附属医院医务部,昆明市650032 [2]昆明医学院第三附属医院麻醉科 [3]昆明医学院第一附属医院麻醉科,昆明市650032

出　　处：《临床麻醉学杂志》2008年第4期334-336,共3页Journal of Clinical Anesthesiology

摘　　要：目的研究神经元缺血-再灌注时诱导型一氧化氮合酶(iNOS)源性一氧化氮(NO)诱导神经元凋亡的信号转导通路。方法培养7d的大鼠海马神经元随机分为四组:正常培养组(A组)神经元按正常培养方法培养;缺血-再灌注组(B组)神经元进行缺糖缺氧后复糖复氧处理;缺血-再灌注+1400W(iNOS抑制药)组(C组)和缺血-再灌注+U-0126(ERK抑制药)组(D组)神经元进行缺糖同时分别加入1400W或U-0126,使其终浓度均为10μM后同B组处理。进行神经元纯度鉴定,检测神经元存活率、神经元凋亡率、NO、cGMP、iNOS-mRNA表达、ERK1/2和P90RSK蛋白表达。结果与A组比较,B组大鼠海马中NO、cGMP、iNOS-mRNA、ERK1/2、P90RSK增高,神经元存活率降低、凋亡率升高(P<0·01)。与B组比较,C组大鼠海马中NO、cGMP、iNOS-mRNA、ERK1/2和P90RSK降低,神经元存活率升高、凋亡率降低(P<0·01);D组大鼠海马中NO、cGMP和iNOS-mRNA变化不明显但ERK1/2和P90RSK降低,神经元存活率升高、凋亡率降低(P<0·01)。结论神经元缺血-再灌注损伤时,iNOS源性的NO通过cGMP介导ERK1/2/P90RSK信号转导通路诱导神经元的凋亡。Objective To investigate the role of cell signal pathway in NO-induced apoptosis after neuron ischemia-reperfusion （I/R） injury. Methods The neuron cells from Wistar rets hippocampus were cultured for 7 days and divided into 4 groups . The cells in group A were treated with a conventional culture way as the controls. The cells in group B were treated with oxygen glucose deprivation（OGD）. The cells in group C were treated with 1 400 W （an inhibitor of inducible nitric oxide synthase,iNOS）, and those in group D with U-0126 10 M during OGD. Neuron viability and apoptosis ,concentrations of NO and cGMP were measured. The expression of iNOS-mRNA, ERK1/2 and P^90RSK protein were detected. Results Compared with group A, NO, cGMP, iNOS-mRNA, ERK1/2 and P^90RSK increased, neuron viability decreased and neuron apoptosis increased in group B （P〈0.01）. Compared with group B, NO,cGMP,iNOS-mRNA,ERK1/2,P^90RSK and neuron apoptosis decreased,neuron viability increased in group C （P〈0.01）, and ERK1/2 , P^90RSK and neuron apoptosis decreased, neuron viability increased, but NO, cGMP and iNOS-mRNA were not significantly changed in group D （P〈0.01）. Conclusion NO induces neuron apoptosis after I/R through eGMP activating ERK/ P^90RSK cell signal pathway.

关 键 词：一氧化氮 ERK1/2 细胞信号转导 缺血-再灌注损伤 凋亡 神经元 

分 类 号：R741[医药卫生—神经病学与精神病学]